Case Of Parathyroid Carcinoma Research Articles

Parathyroid carcinoma: molecular pathology and correlation with clinicopathologic features, a single center experience

Abstract Introduction/Objective Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single center regarding the clinic-pathologic and genetic analysis of parathyroid carcinoma cases. Methods/Case Report The study is a retrospective review of all patients with parathyroid carcinoma that were evaluated at a tertiary oncologic center from 2001 until 2023. Results (if a Case Study enter NA) A total of nine cases (6 male and 3 female) were identified, with a mean age at diagnosis of 52 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 7), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and a mean PTH of 1123 pg/ml (<a href=“tel:276- 2500”>276-2500</a>). En bloc surgical resection was performed in 6 patients and 3 patients underwent adjuvant radiotherapy. Recurrence was observed in 4 cases (44.4%) after a median of 24 months following surgery. Negative immunohistochemical staining of parafibromin was noted in 3/4 cases of recurrence. Parathyroid carcinoma was diagnosed on the basis of finding lesions with vascular or perineural invasion, capsular penetration, and/or documented metastases. Immunohistochemical staining for parafibromin, Ki-67, and E-cadherin was performed on formalin-fixed, paraffin-embedded tissue samples. Next generation sequencing (NGS) was performed in 6/9 cases and CDC73 mutations were present in 38.5% of analyzed patients. Loss of TP53 and RB1 alleles and CCND1 amplification were other reported genetic alterations in the study cohort. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Inactivating CDC73 alterations which include truncating or frameshift mutations, as well as missense mutations lead to the loss of parafibromin immunoreactivity. Other molecular alterations like PTEN and PIK3CA mutations may represent potential targets for molecular therapy. An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish parathyroid carcinoma from other parathyroid neoplasms.

12313 Parathyroid Carcinoma Presenting As Right Foot Pain And Swelling In A Young Male - A Case Report

Abstract Disclosure: F.E. Sorsona: None. L. Lopez: None. Parathyroid carcinoma is a rare cause of hyperparathyroidism that is challenging to diagnose. We report a case of parathyroid carcinoma with an unusual initial presentation of right foot pain and swelling in a young 26-year-old Filipino male. Physical examination revealed a palpable 1 x 1 cm mass with tenderness on his right foot. Initial work-up showed a persistently elevated serum ionized calcium (range: 1.7 - 2.19 mmol/L) with markedly high intact parathyroid hormone (1,890 pg/ml). A right foot x-ray revealed a lytic bone lesion on the 3rd metatarsal. Skeletal survey revealed diffuse lytic bone lesions. Comprehensive neck ultrasound showed a 4 x 1.6 x 2.5 cm complex nodule adjacent to the inferior pole of the left lobe of the thyroid gland with intralesional calcifications. A 4D CT scan showed a 3.3 x 2.2 x 2 cm hypervascular nodule inferior to the left thyroid lobe with early contrast washout, likely parathyroid in origin, and a possible brown tumor in the right fourth rib. Patient underwent parathyroidectomy with intraoperative PTH monitoring showing a marked reduction of intact PTH by 87% (235.9 pg/ml from 1,890 pg/ml), accompanied by reduction of serum ionized calcium. The histopathology reported parathyroid carcinoma highlighted by lymphovascular invasion, atypical round cells in sheets and nests, with enlarged, mildly pleomorphic, hyperchromatic nuclei and prominent nucleoli. Two months after surgery, normal serum ionized calcium was maintained with calcium supplementation with reported relief of right foot pain and swelling. The patient continues to follow up regularly for monitoring of treatment response. Presentation: 6/2/2024

7388 Rare Case of Mediastinal Parathyroid Carcinoma

Abstract Disclosure: Y. Esaki: None. J. Moalem: None. A. Israel: None. I. Shafiq: None. Introduction: Parathyroid carcinoma accounts for 1% of primary hyperparathyroidism with an estimated prevalence of 0.005% of all cancers. Ectopic locations of parathyroid tumors have been found in 6-16% of cases, most commonly in the thyroid, the thymus, or behind the esophagus. Parathyroid carcinoma is rarely found in the mediastinum and only 30 cases have been reported in the literature. Clinical Case: A 68-year-old male without significant past medical history was evaluated by his primary care physician for constipation, polyuria and 20 lb weight loss over the past year. He presented to the hospital after blood work revealed serum calcium of 13.5 mg/dl (8.6-10.2 mg/dl). Initial hospital workup demonstrated serum calcium 12.9 mg/dl, phosphorus 2.6 mg/dl (2.7-4.5 mg/dl), 25-OH vitamin D 21 ng/ml (30-60 ng/ml), 1,25-(OH)2 vitamin D 143.0 pg/ml (19.9-79.3 pg/ml), PTH-related protein < 2.0 pmol/L (0.0-2.3 pmol/L) and PTH 1,250.0 pg/ml (15.0-65.0 pg/ml). CT scan revealed a 3.5 cm x 2.6 cm heterogeneous right paratracheal soft tissue mass with areas of calcifications with mass effect on SVC. Thyroid ultrasound showed multinodular thyroid tissues with a left 1.1 cm heterogeneous solid nodule along the mid posterior aspect as well as a 0.5 cm hypoechoic lesion inferior to the left lobe. Sestamibi scan demonstrated a large area of increased uptake corresponding to the mass seen in the superior mediastinum on CT imaging. He underwent neck exploration and left hemithyroidectomy as well as median sternotomy with resection of the paratracheal mass. Intraoperative PTH decreased from the baseline of 1,177.0 pg/ml to 65.6pg/ml following the removal of the paratracheal mass. The final pathology of right anterior mediastinal mass was consistent with a 5 cm parathyroid carcinoma with angioinvasion, intermediate lymphatic invasion, invasion into adjacent structures, and Ki67 proliferative index focally > 5%. His post-operative course was complicated by hypocalcemia, which improved with treatment with calcitriol and calcium supplementation. He declined the genetic testing. His calcium and parathyroid hormone have remained in the normal range after 1 year. Conclusion: This case illustrates a rare case of parathyroid carcinoma found in the mediastinum. It is important to recognize that parathyroid carcinoma can present in ectopic locations including the mediastinum, as this can affect the preoperative investigation and management. Fine needle biopsy (FNA) prior to the initial operation is not recommended as it is difficult to differentiate the parathyroid carcinoma from benign disease based on FNA, and it may cause tumor rupture and seeding. Also, in the mediastinal parathyroid carcinoma, localization of the lesions including the size and invasiveness is critical in order to allow for radical surgery. Presentation: 6/3/2024

7191 When Pain Is Misdiagnosed: A Case of Parathyroid Carcinoma Masked as Fibromyalgia

Abstract Disclosure: H. Pham: None. P.V. Kumar: None. S. Taylor: None. Parathyroid carcinoma is a rare and aggressive cause of hyperparathyroidism, typically associated with <1% of primary hyperparathyroidism cases. Incidence occurs mainly in the 5th decade of life, with less than 4% of all cases presenting in patients under age 30. Here, we highlight a case involving a 28-year-old woman with fibromyalgia who presented for worsening right shoulder pain in the setting of progressive, poorly characterized pain for the past year. Her initial physical exam was unremarkable aside from a non-tender left sided neck enlargement. However, her laboratory results were significant for corrected serum calcium of 15 mg/dL, serum phosphorus of 2.3 mg/dL, parathyroid hormone (PTH) >2500 pg/mL, and alkaline phosphatase 1604 units/L. X-ray of her right shoulder demonstrated mottled bone concerning for degenerative disease. Thyroid ultrasound revealed a complex cystic lesion posterior to the left thyroid lobe measuring 5.3 x 3.9 x 2.9 cm, worrisome for giant parathyroid adenoma. CT abdomen/pelvis showed diffuse osteosclerosis and innumerable lytic lesions, consistent with osteitis fibrosa cystica, as well as bilateral nephrolithiasis, likely medullary nephrocalcinosis. Her hypercalcemia was treated with aggressive hydration with normal saline and IV pamidronate. She underwent surgical resection of her parathyroid adenoma, which was unfortunately complicated by symptomatic hypocalcemia requiring prolonged care in the ICU. Her calcium levels did improve within a few days, and she was subsequently discharged with close outpatient follow-up. Final pathology report showed predominant thickened trabecular growth pattern with focal vascular invasion consistent with parathyroid carcinoma. Our patient’s case represents a rare presentation of parathyroid carcinoma in a young patient without any additional risk factors. Although atypical, her severe symptomatic hypercalcemia, nephrolithiasis, presence of large neck mass, and diffuse skeletal disease warranted immediate concern for malignant hyperparathyroidism instead of benign adenoma. Delayed diagnosis in our patient led to prolonged bone disease and severe complications. While hungry bone syndrome typically manifests post-parathyroidectomy in patients with end-stage renal disease, our patient experienced this complication in the setting of advanced, untreated hyperparathyroidism. We should consider hypercalcemia and hyperparathyroidism in our differential diagnosis for chronic pain, especially if pain remains uncontrolled with conservative measures. The most appropriate initial test for evaluation of hypercalcemia is a PTH level to distinguish between PTH-dependent and PTH-independent etiologies. Parathyroid carcinoma, even in young patients, should be considered when PTH is >3x upper limit of normal, serum calcium is >14, or skeletal and renal involvement is present. Presentation: 6/3/2024

Parathyroid Carcinomas: A Series of 6 Cases and Literature Review

Parathyroid carcinoma (PC) is a rare endocrine malignancy. We report 6 cases of PCs operated on in our department, during a period of 12 years (2010-2021). All of our patients presented severe hyperparathyroidism, high calcium levels, and very elevated parathormone (PTH) rates. Five were between the fifth and sixth decades of life and 1 patient was 37 years old. The parathyroid gland was only palpable in 1 case. All of our patients underwent cervical ultrasound and 5 of them underwent 99m Tc-MIBI scintigraphy. One of the patients presented bilateral parathyroid masses. All our patients were treated surgically: a parathyroidectomy was performed in all cases. In 1 patient, parathyroidectomy was performed in conjunction with a homolateral loboisthmectomy, as the diagnosis of PC was suspected preoperatively due to pulmonary metastases. The final anatomopathological study revealed PC in all cases. Follow-up was uneventful in 5 cases and 1 patient was lost to follow-up. Clinicians should suspect PC in patients with severe hypercalcemia, extremely elevated PTH levels, large parathyroid lesions, and distant metastases. Complete surgical resection, extended to the homolateral thyroid lobe, remains the recommended treatment.

Immunotherapy for endocrine tumours: a clinician's perspective.

Immunotherapy has revolutionised the treatment of oncological patients, but its application in various endocrine tumours is rather limited and is mainly used when conventional therapies have failed. Immune checkpoint inhibitors (ICIs) have been employed in progressive adrenocortical carcinoma, primarily utilizing the anti-PD-L1 agent pembrolizumab, obtaining overall response rates ranging between 14% and 23%. In contrast, the response rate in phaeochromocytoma/paraganglioma was substantially less at 9%, considering the small number of patients treated. Similarly, the response rate in advanced differentiated thyroid carcinomas treated with pembrolizumab was also low at 9%, although the combination of ICIs with tyrosine kinase inhibitors showed higher efficacy. Low response rates to ICIs have also been observed in progressive medullary thyroid cancer, except in tumours with a high mutation burden (TMB). Pembrolizumab or spartalizumab can be utilized in patients with high TMB anaplastic thyroid cancer, obtaining better response rates, particularly in patients with high PD-L1 expression. Immunotherapy has also been used in a few cases of parathyroid carcinoma, showing limited antitumour effect. Pituitary carcinomas may exhibit a more favourable response to ICIs compared to aggressive pituitary tumours, particularly corticotroph tumours. Patients with advanced neuroendocrine tumours achieve an overall response rate of 15%, which varies according to the primary tumour site of origin, degree of differentiation, and therapeutic regimen utilised. Future research is needed to evaluate the potential role of immunohistochemical biomarkers, such as programmed death 1/programmed death ligand 1 and TMB, as predictors for the response to immunotherapy. Furthermore, randomised prospective studies could provide more robust data on the efficacy and side effects of ICIs.

O-13 Parathyroid carcinoma - a rare and challenging entity

Abstract Background Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of all cases of primary hyperparathyroidism (HPT). This entity affects both men and women equally and is usually diagnosed in the fourth or fifth decade of life. It can occur sporadically or be associated with genetic syndromes such as hyperparathyroidism-jaw tumor syndrome. Its clinical presentation can overlap with that of primary HPT, with hypercalcemia that can lead to a range of symptoms, such as fatigue, weakness, bone pain, kidney stones, and gastrointestinal disorders. Distinguished by its rarity and clinical challenges, this condition requires a high level of suspicion and its initial surgical approach correlates with long-term prognosis. Clinical Case This is the case of a male patient, 39 years old, Caucasian, with a previous history of hypertension diagnosed 5 months earlier, deep vein thrombosis (DVT) diagnosed 2 months earlier, and active tobacco use. Additional study performed after the DVT episode found severe hypercalcemia (14.3 mg/dL, N 8.6-10.0), hypophosphatemia (2.2 mg/dL, N 2.5-4.5), and renal dysfunction (Creatinine 1.43 mg/dL). The patient was asymptomatic and was admitted to the Internal Medicine department, to correct the hypercalcemia and further investigation. Increased PTH levels (1555 pg/mL, N 15-65) were found, and a cervical ultrasound revealed, on the left thyroid lobe, a bilobed nodule, mainly solid, hypoechogenic, with irregular margins and macrocalcifications, with 34×22 mm. Full body CT showed osteolytic lesions on several ribs and both iliacs and kidney stones. A bone scintigraphy was also done, showing a diffuse fixation on the axial and appendicular skeleton, compatible with diffuse osteomedullary infiltration. Due to these findings, the collaboration of the Endocrinology department was requested. Based on the PTH levels and the characteristics of the cervical mass, suspicion arose regarding a potential case of parathyroid carcinoma. Subsequently, a parathyroid scintigraphy using Sestamibi was conducted, whose report revealed an intense hyperfixation at a nodular formation projecting on the lower two-thirds of the thyroid left lobe, without unequivocal identification of its origin - thyroid nodule vs. parathyroid tissue. Based on intraoperative findings and clinical suspicion, en bloc resection of the tumor along with the thyroid lobe and unilateral neck exploration was performed by the Surgery department, with the pathological assessment confirming the malignancy diagnosis. The patient was referred to an oncologic tertiary center, for follow-up and genetic testing. Conclusion We want to shed light on this rare entity and the importance of multidisciplinary critical thinking, alongside imaging. Markedly elevated PTH and/or calcium levels on a patient with a cervical mass should arouse suspicion of a parathyroid carcinoma, which must not be biopsied and warrants a more extensive surgery to ensure the best possible prognosis.

Functional and nonfunctional parathyroid carcinoma: two case reports and literature review

Parathyroid carcinoma (PC) is a rare malignant endocrine tumor. It can be divided into functional and non-functional types according to the tumor’s ability to secrete parathyroid hormone. Herein, we present a case each of functional and nonfunctional PC. Case 1: Functional PC. The main clinical symptoms were high parathyroid hormone and hypercalcemia with bone injury and other complications. The mass was large, capsulated, and showed vascular invasion. The tumor was surgically removed, along with a part of the tracheal wall and recurrent laryngeal nerve that were invaded by the tumor. The ipsilateral and isthmus thyroid lobe and central lymph nodes were also removed. Medicines were given to lower blood calcium. The patient died 18 months after surgery because of severe pulmonary infection and tracheal stenosis. Case 2: Non-functional PC. The patient showed no obvious clinical symptoms, but physical examination revealed a thyroid nodule. Despite the small diameter, the mass still invaded the surrounding thyroid lobe, fat, and muscle tissue. Surgery was performed to remove the tumor and ipsilateral thyroid lobe and central lymph nodes. The patient survived without recurrence or metastasis. Thus, we believe that the prognosis of PC negatively correlates with the scope of surgery. Early surgery can improve patient prognosis, and physical examination is conducive to early detection of PC. Herein, we provide a description of the diagnostic workup and the treatment approach and review relevant studies. We summarize the clinicopathological characteristics of PC cases to provide evidence for early diagnosis and therapy, to improve patient prognosis.

SAT205 99Technitiumm Sestamibi Negative Sporadic Metastatic Parathyroid Carcinoma In A Young Female-A Diagnostic Conundrum

Abstract Disclosure: D.V. Reddy: None. S. Paidipally: None. V. kyatham: None. S. Palle: None. C. Bhandiwad: None. Background: Parathyroid carcinoma (PC) is a very rare and indolent endocrine malignancy occurring a decade earlier than parathyroid adenoma. It can present as recurrent pancreatitis, anemia, and peptic ulcers. Serum calcium >14mg/dl, 3-10 times ULN of PTH, and concomitant renal and bone involvement should arise suspicion for PC. PC is diagnosed only through histopathology in the majority. It can also present during a prolonged follow-up, either by local recurrences or distant metastases. Clinical Case: A 27 year old female presented with hypercalcemic crises (as pancreatitis). At admission serum calcium and PTH were grossly elevated; 15.1 mg/dl (8.5-10 mg/dl) and 363 pg/ml (10-55 pg/ml) respectively. Abdominal CT revealed acute pancreatitis with medullary nephrocalcinosis. Ultrasonography of the neck revealed a colloid cyst in the right lobe of thyroid.99Tc m-sestamibi /SPECT-CT revealed no uptake. CT neck and chest showed a 13 mm X 13 mm well-defined round nodular lesion in the left apico-posterior segments of the lung. 18F-FDG PET/CT revealed uptake in the lesion with an SUV max of 10, suggestive of a metabolically active solitary pulmonary nodule. She had a similar presentation 8 years back and was diagnosed to have parathyroid adenoma for which she underwent resection. Serum PTH and calcium levels normalized postoperatively and also on follow-up till 3 years. Differentials include-recurrent ectopic parathyroid adenoma, parathyromatosis, and metastatic parathyroid carcinoma. After managing hypercalcemia medically, the patient underwent video-assisted thoracoscopic surgery with left lung wedge resection. Postoperatively serum calcium and PTH normalized. Histopathology revealed a grey-white nodule of 1.4X1.5X1.2 cm with sections, showing a well-defined lesion composed of lobules and nests of tumor cells separated by thin-walled vascular sinusoids. Tumor cells were polygonal with well-defined margins, moderate granular cytoplasm, and vesicular nuclei showing prominent nucleoli with a mitotic activity of 9/hpf. Immunohistochemistry revealed staining with PanCK, GATA3, and S100 with focal PAX 8 activity in the periphery. MIB index was 18%.IHC was suggestive of a neuroendocrine tumor consistent with metastatic parathyroid carcinoma. Whole exome sequencing did not reveal any pathogenic variants. Conclusion: Though 99Tc MIBI is useful in localizing PC, there are reports of false negative MIBI in documented cases of PC, which has been ascribed to the defective transport to the interior of the malignant cells. This demonstrates the importance of a multimodality imaging approach in such cases. 99Tc MIBI may miss certain cases of PC substantiating the importance of 18F-FDG PET/CT in diagnosis as well as follow-up. Reference: Evangelista L et al. FDG-PET/CT and parathyroid carcinoma: Review of literature and illustrative case series. World J Clin Oncol 2011; 2(10): 348-354. Presentation: Saturday, June 17, 2023

Clinical and molecular characterization of parathyroid carcinoma in multiple endocrine neoplasia type 1.

Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4-10.2) and 472 pg/mL (12-65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

Casuistic cases of parathyroid carcinoma with a verified mutation in the MEN1 gene

Parathyroid cancer (PTC) is usually sporadic; however, it could be presented as a component of hereditary syndromes. The prevalence of PTC among patients with primary hyperparathyroidism (PHPT) is about 1% cases. The lack of reliable preoperative predictors significantly complicates the diagnosis of PTC. The clinical course is non-specific and in most cases is determined by severe hypercalcemia. The final diagnosis can only be made on the basis of invasive histopathologic features, while an analysis immunohistochemical (IHC) one can be used only as an additional method. Given the rarity the diagnosis of MEN1-related PTC a challenge. We present two clinical cases of patients with PTC and a verified heterozygous mutation in the MEN1 gene. The described cases demonstrate the complexity of morphological diagnosis for PTC, the heterogeneity of clinical manifestations in patients with the MEN1 mutation, as well as the need for timely screening to identify other components of MEN1 syndrome and mutations of the MEN1 gene among first-line relatives.

Parathyroid Cancer—A Rare Finding during Parathyroidectomy in High Volume Surgery Centre

Background and Objectives: Parathyroid cancer is a very rare endocrine tumor, especially in patients with secondary hyperparathyroidism due to end stage renal disease failure. This pathology is difficult to diagnose preoperatively because it has nonspecific clinical manifestations and paraclinical aspects. Our study of the literature identified 34 reported cases of parathyroid carcinoma over the last 40 years in patients undergoing dialysis. We present our experience as illustrative of the features of clinical presentation and histopathological findings of parathyroid carcinoma and assess its management considering the recent relevant literature. Materials and Methods: From January 2012 to November 2022, 650 patients with secondary hyperparathyroidism undergoing dialysis were treated at our academic Department of General Surgery and only two cases of parathyroid carcinoma were diagnosed on histopathological examination. Results: All patients presented with symptomatic hypercalcemia, with no clinical or imaging suspicion of malignant disease and were surgically treated by total parathyroidectomy. Histopathological examination revealed morphologic aspects of parathyroid carcinoma in two cases and immunostaining of Ki-67 was performed for diagnostic confirmation. Postoperative follow-up showed no signs of recurrence and no oncological adjuvant treatment or surgical reinterventions were needed. Conclusions: Parathyroid neoplasia is a particularly rare disease, that remains a challenge when it comes to diagnosis and proper management. Surgical approach is the only valid treatment to remove the malignant tissue and thus improve the patient's prognosis. Medical and oncologic treatment may be beneficial to control hypercalcemia in case of tumor recurrence.

Parathyroid carcinoma with pancreatitis causing hypercalcaemic emergency treated with extracorporeal membrane oxygenation-assisted parathyroid resection.

Emergencies due to malignancies usually have a severe clinical course and require urgent treatment. These scenarios are dubbed 'oncologic emergencies'. Parathyroid tumours often cause hypercalcaemia but not oncologic emergencies. We present a case of parathyroid carcinoma with severe hypercalcaemia and pancreatitis, resolved by surgical resection of the tumour assisted by extracorporeal membrane oxygenation (ECMO). A 66-year-old woman presented to our hospital because of haematuria. Laboratory findings were as follows: white blood cell count: 30 000, C-reactive protein: 17.7, calcium: 21.9, creatine kinase: 316, creatine kinase-myoglobin binding: 20, troponin I: 1415.8, amylase: 1046, lipase: 499, blood urea nitrogen: 57, and creatinine: 2.42. ECG was unremarkable. CT revealed a 4-cm low-density irregular tumour in the left lobe of the thyroid gland and severe pancreatitis. We diagnosed hypercalcaemia and pancreatitis due to parathyroid carcinoma. Volume expansion with isotonic saline was started immediately. Calcitonin, followed by denosumab, calcimimetic agents, and continuous hemodiafiltration were administered. The patient's general condition worsened due to uncontrolled hypercalcaemia. Urgent tumour resection was planned, assisted with ECMO for cardiopulmonary support and surgical field venous pressure reduction. Tumour histology was suggestive of parathyroid carcinoma. Hypercalcaemia and the patient's general condition improved gradually postoperatively. Hypercalcaemia is one of the oncologic emergency symptoms, commonly occurring because of lytic bone metastasis. However, reports about parathyroid carcinoma-causing life-threatening hypercalcaemia and pancreatitis are scarce; the fatality of this condition is estimated to be 30-70%. We report a case of survival of hypercalcaemia of malignancy. Parathyroid carcinoma is relatively rare and sometimes causes emergent conditions such as hypercalcaemia and severe pancreatitis. General therapy for hypercalcaemia including aggressive saline dehydration, administration of furosemide, calcitonin, zoledronic acid, and evocalcet, and dialysis is sometimes ineffective for parathyroid carcinoma. Therefore, careful planning of therapy in case of exacerbation is important. During an emergency, rapid surgical treatment despite high calcium level is the best potential therapeutic strategy.

Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.

Effect of early dose increase of evocalcet for intractable hypercalcemia caused by parathyroid carcinoma.

Hypercalcemia due to parathyroid carcinoma (PC) is safely and quickly controlled with rapidly increasing evocalcet doses. Most parathyroid carcinomas are detected because of hypercalcemia due to primary hyperparathyroidism (PHPT). Hypercalcemia becomes more severe in patients with PC than those with parathyroid adenoma or hyperplasia. Hypercalcemia often causes renal dysfunction, gastrointestinal symptoms, and psychiatric symptoms. Consequently, the serum calcium level needs to be promptly corrected. Here, we report a case of PC with remarkably persistent hypercalcemia, which we safely and quickly controlled with rapidly increasing evocalcet doses. A 77-year-old female presented with renal dysfunction. Her serum calcium (Ca) and intact parathyroid hormone serum levels were 13.9 mg/dL and 1.074 pg/mL, respectively. Her renal function worsened because of hypercalcemia due to PHPT. Technetium-99 m methoxy-isobutyl-isonitrile parathyroid scintigraphic examination revealed an accumulation below the right thyroid lobe. CT examination showed a 35-mm mass. Hypercalcemia needed to be immediately corrected because of the patient's worsening renal function. Evocalcet treatment at a gradually increasing dose of up to 20 mg over 3 weeks allowed her serum Ca level to be maintained below 11 mg/dL. Only mild nausea was observed at the beginning of the treatment. The mass was suspected as PC because the hypercalcemia was refractory to high-dose evocalcet. The patient was treated with parathyroidectomy and ipsilateral thyroidectomy. PC was diagnosed based on the pathological findings of capsular and venous invasion. The patient's renal function improved and surgery could be safely performed by promptly correcting hypercalcemia. Hypercalcemia due to parathyroid carcinoma (PC) is often more severe than that caused by parathyroid adenoma or hyperplasia. PC is a rare disease, but it should be considered if the patient has intractable hypercalcemia due to primary hyperparathyroidism (PHPT). Evocalcet, which is used to treat hypercalcemia due to PHPT, does not interact with P450 (CYP) and causes few side effects. Complications, including renal dysfunction, were improved and the surgery could be safely performed by promptly correcting hypercalcemia. PC has a high recurrence rate. En-block excision is necessary when PC is suspected.

Design and development of a European registry for parathyroid carcinoma cases within the scope of the European Registries for Rare Endocrine Conditions (EuRRECa)

Parathyroid carcinoma (PC) is an extremely rare malignant endocrine tumor of the parathyroid glands. Given the extreme rarity of this cancer, many issues regarding its diagnosis, prognosis, clinical management, and tumor-derived complications remain unresolved, and no standardized protocol has yet been defined for its diagnosis. As with all rare clinical conditions, the creation of multicenter national databases and international registries is fundamental in order to collect data on a relatively high number of PC cases and increase knowledge of this rare parathyroid condition, with the ultimate aim of identifying potential factors that influence its diagnostics, natural course, prognosis, skeletal complications, and treatment. In this light, the “parathyroid carcinoma working group” (https://eurreca.net/parathyroid-carcinoma/) designed and developed a specific PC module within the scope of the European Registries for Rare Endocrine Conditions (EuRRECa). The module, finalized and launched at the end of 2022, is now available online to collect data on PC cases. Users must first request access to the e-Reporting of Rare Conditions system (e-REC) and obtain their personal login credentials.

RF05 | PSUN364 A Rare Case of Bilateral Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 1

Abstract Background Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder classically characterized by parathyroid gland tumors, anterior pituitary adenomas, and tumors of the gastro-entero-pancreatic tract. The majority of MEN1 cases involving lesions of the parathyroid gland causing hyperparathyroidism are almost always benign. It is extremely rare for hyperparathyroidism to be caused by parathyroid carcinomas. We report a very rare case of parathyroid carcinoma presenting in MEN1 syndrome. Case Report We present the case of a 45 year old male with a history of untreated hypertension, nephrolithiasis, and CKD, who became suddenly unresponsive, was intubated, and found to have a severe acute intraparenchymal hemorrhage secondary to severe hypertension on Head CT. Secondary causes of hypertension were ruled out, with renin activity, aldosterone levels, and urine metanephrines unremarkable; abdominal ultrasound with doppler was also negative for renal artery stenosis. Stroke protocol was initiated, with CTA Head negative for any acute findings. However, CTA Neck showed bilateral large nodules posterior to the thyroid lobes measuring 4.0×3.2 cm on the right and 3.9×2.5 cm on the left, with mass effect on the thyroid and adjacent carotids. Routine labs showed hypercalcemia of 13.3 (8.4-10.2 mg/dL) in the setting of elevated PTH levels of 1085 (15-65 pg/mL), with repeat PTH level of 1106 confirming primary hyperparathyroidism. Other causes of hypercalcemia were investigated, with levels of Calcitonin and Calcitriol/1,25 vitamin D within normal limits, but a decreased level of 25 hydroxy vitamin D of <12.8 (30-100 pg/mL). Maxillofacial CT was negative for any ossifying fibromas, ruling out jaw tumor syndrome. CT Abdomen showed hyperdense nodular areas in the pancreas, and MRI Brain was negative for any discrete pituitary gland lesions. Thyroid US was performed and revealed mixed cystic and solid masses posterior to both lobes of the thyroid; as a result, FNA of the thyroid and posterior mass was done, confirming hypercellular parathyroid tissue and benign thyroid tissue. Due to high suspicion for parathyroid carcinoma, the patient underwent a parathyroidectomy, with pathology confirming bilateral parathyroid carcinoma. Genetic testing was positive for MEN1, with a frameshift variant mutation of c.1299_1312del (p.Val434Leufs*10). Conclusion This is a very rare case of bilateral parathyroid carcinoma presenting in MEN1. To the best of our knowledge, this genetic mutation has not been reported in online databases or published literature. The clinical presentation of parathyroid lesions and pancreatic nodules in the setting of hypercalcemia should prompt further evaluation of genetic disorders such as MEN1. In this context, it is essential that MEN1 patients be managed with a multidisciplinary approach given the disorder's complexity of diagnosis and treatment. Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT198 Atypical Parathyroid Adenoma is an Unusual Cause of Primary Hyperparathyroidism

Abstract Background Atypical parathyroid adenomas (APA) are considered tumors of uncertain malignant potential and have a biochemical and clinical phenotype that is generally more aggressive than typical parathyroid adenomas (PA). Low incidence as an etiology of primary hyperparathyroidism (PHPT) presents a challenge in understanding the pathological features and natural history of APA. We present a case of PHPT due to an APA and review the published literature for these tumors. Case A 37 year-old male was referred for evaluation of hypercalcemia, with serum calcium level 13.6 mg/dL (8.6-10.3). Repeat serum calcium measurement was 12.7 mg/dL, and two measurements of intact PTH were 870 pg/mL and 919 pg/mL (12-88), respectively. The patient's laboratories raised concern for parathyroid carcinoma (PC), but there was no palpable neck mass and no enlarged parathyroid glands were visualized on ultrasonography. Parathyroid scintigraphy was notable for faint but persistent Tc-99 m sestamibi uptake in the left inferior neck. Additional preoperative evaluation revealed significantly reduced bone mineral density in the distal third of the radius (0.638 g/cm2, Z-score -3.2), silent nephrolithiasis of the right kidney, and vitamin D deficiency (25-OH vitamin D 13.4 ng/dL, 30-100). An unequivocally enlarged (175 mg, 2.5 cm in largest diameter) left inferior parathyroid gland was removed, with the remaining glands unremarkable by inspection. Extensive nuclear atypia and cellular pleomorphism indicated an APA, and invasive features of PC were absent. One month after surgery, serum calcium improved to 10.2 mg/dL and intact PTH was 40 pg/mL. Conclusions APA account for 1-2% of PHPT cases. This patient's case has several features that distinguish it from a PA including degrees of preoperative hypercalcemia and intact PTH elevation, low vitamin D level, significantly reduced bone density in the distal third of the radius, nephrolithiasis, relatively young age, and male gender. Fibrous bands, pseudocapsular invasion, and trabecular growth pattern are the most common histologic features of APA, but nuclear atypia and cellular pleomorphism are well established diagnostic criteria. APA may be biochemically similar to PC but are distinguished from PC by the absence of gross invasion into adjacent anatomic structures, distant metastases, and vascular or perineural invasion. Additionally, CDC73 mutations are present in nearly all cases of PC but not in APA. Over 90% of patients with APA are successfully treated by parathyroidectomy. Careful follow up of APA patients is recommended, though there are no specific guidelines regarding a minimum satisfactory duration of postsurgical monitoring. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Association of Parathyroid and Differentiated Thyroid Carcinomas: A Narrative Up-To-Date Review of the Literature.

Aim: Parathyroid carcinoma (PC) is a rare endocrine malignancy that represents 0.005% of all malignant tumors. Associated PC and differentiated thyroid carcinoma (DTC) is an exceptionally rare condition, and the preoperative diagnostics and proper treatment are challenging. Almost all PCs and the majority of DTCs are diagnosed postoperatively, making correct surgical treatment questionable. Specific guidelines for parathyroid and thyroid carcinomas association treatment are lacking. The purposes of our study were to identify the association between parathyroid and thyroid carcinomas, to analyze the available published data, and to evaluate the possible relationship between preoperative diagnostic and surgical decision-making, and outcome-related issues. Material and methods: We performed a literature review of several databases from the earliest records to March 2022, using controlled vocabulary and keywords to search for records on the topic of PC and WDTC pathological association. The reference lists from the initially identified articles were analyzed to obtain more references. Results: We identified 25 cases of PC and DTC association, 14 more than the latest review from 2021. The mean age of patients was 55, with a female to male ratio of about 3:1. Exposure to external radiation was identified in only one patient, although it is considered a risk factor the development of both PC and DTC. The preoperative suspicion of PC was stated by the authors in only 25% of cases, but suspicion based on clinical, laboratory, ultrasound (US), and fine needle aspiration (FNA) criteria could have been justified in more than 50% of them. With neck ultrasound, 40% of patients presented suspicious features both for PC and thyroid carcinoma. Intra-operatory descriptions of the lesions revealed the highest suspicion (83.3%) of PC, but en bloc resection was recommended and probably performed in only about 50% of the cases. Histopathological examinations of the thyroid revealed different forms of papillary thyroid carcinoma (PTC) in most cases. Postoperative normocalcemia was achieved in 72% of patients, but follow-up data was missing in about 25% of cases. Conclusion: Associated PC and DTC is an exceptionally rare condition, and the preoperative diagnostic and treatment of the patients is a challenge. However, in most cases pre- and intraoperative suspicious features are present for identification by a highly specialized multidisciplinary endocrine team, who can thus perform the optimal treatment to achieve curability.

Case series of diagnosis and surgery challenges in parathyroid carcinoma.

IntroductionParathyroid carcinoma (PC) is a rare malignancy that accounts for 1 % of cases of hyperparathyroidism. Data regarding PC in Indonesia are scarce, which poses challenges to diagnosis and treatment. This study aims to describe a series of PC cases from a tertiary health care center over 12 years.Presentation of casesRetrospective data of six patients with hyperparathyroidism diagnosed with PC between 2008 and 2020 were reviewed. Clinical presentation, diagnosis, management, and short-term outcomes of PC were analyzed. All six PC patients were diagnosed postoperatively. Four of the patients presented with symptomatic hypercalcemia, and two presented with neck swelling. Elevated serum parathyroid hormone was observed in five patients. Only two patients had imaging results corresponding to PC characteristics. Ipsilateral parathyroidectomies were performed on 5 patients where invasion and metastasis are not evident. Four frozen section samples suggested PC, and two suggested parathyroid adenoma. Further histopathologic examination confirmed a diagnosis of PC in all patients. No metastasis to the adjacent lymph nodes or distant target organs was found during surgery.DiscussionPreoperative diagnosis of PC remains challenging. Suspicion of PC is appropriate in the presence of severe hypercalcemia, elevated parathyroid hormone level, and a mass observed either during imaging or intraoperatively.ConclusionIpsilateral parathyroidectomy seems to be feasible compared to total resection in order to preserve function and structure. Incomplete excision may lead to an increased risk of recurrence, emphasizing the importance of routinely following up on PC cases.